Session Time: 3:15pm-4:45pm
Presentation Time: 3:15pm-3:27pm
*Purpose: MicroRNAs (miRNAs) are small noncoding RNAs which regulate mRNA expression at the posttranscriptional level. We investigated blood miRNAs as non-invasive biomarkers in kidney transplantation as part of the BIOMARGIN consortium (ClinicalTrials.gov, number NCT02832661).
*Methods: Blood samples were collected at time of the 717 renal allograft biopsies, in four European transplant centers. Both mRNAs and miRNAs were quantified in a multistage discovery-to-validation study. Primary end point was the diagnostic accuracy of a multiple miRNAs biomarker for antibody-mediated rejection (ABMR), assessed in 453 unselected and consecutively collected samples. Secondary endpoints were: (i) to evaluate the accuracy of an ABMR diagnostic tool including the miRNA-signature combined to clinico-biological data, (ii) to study the cellular origin of the selected miRNAs and their pathophysiological implication. For the latter, PBMCs were collected from healthy donors and transplant recipients and miRNAs expression was quantified in different PBMC subsets.
*Results: We identified a 3-miRNA signature (miR-15b, miR-106a, miR-374a) which yielded an AUC of 70.4% (95% confidence interval [CI], 61.6 to 79.1; p<0.0001) for the diagnosis of ABMR. Combined with proteinuria and donor-specific antibodies, the model yielded an AUC of 85.3% (95% CI, 77.9 to 92.8; p<0.0001). The expression of the 3 miRNAs was significantly decreased in ABMR patients suggesting an increased expression of their targeted mRNAs. Intersection of these targeted genes with the whole transcriptome data (panel A) showed indeed that up to 23% of the highly up-regulated mRNAs (fold-change >1) in ABMR cases, were regulated by one of the 3 miRNAs (Panel B). In silico analyses suggested an enrichment in myeloid-derived pathways, and among PBMC subsets, the 3 miRNAs were confirmed to be mainly originating from classical monocytes.
*Conclusions: Together, our data provide new insights in miRNAs as biomarkers as well as key-player in ABMR. The link between monocytes response in the blood and their infiltrating properties in the allograft could provide new insights to pathological mechanisms in ABMR.
To cite this abstract in AMA style:Tinel C, Lamarthée B, Tokarski FVon, Rabant M, Legendre C, Gwinner W, Naesens M, Marquet P, Anglicheau D. A Monocyte-Derived MicroRNA Signature for Antibody-Mediated Rejection in Kidney Transplantation [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/a-monocyte-derived-microrna-signature-for-antibody-mediated-rejection-in-kidney-transplantation/. Accessed April 23, 2021.
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